Levofloxacin-Based Concomitant and Sequential Therapies Perform Equally Against H. pylori in Syrian Trial

A randomized clinical trial conducted in Damascus has found that two widely used antibiotic regimens for eradicating Helicobacter pylori, the bacterium responsible for most peptic ulcers and a major risk factor for gastric cancer, perform almost identically in treatment-naïve Syrian patients. The study, published in the journal Gut Pathogens, compared a 14-day levofloxacin-based concomitant regimen against a 14-day levofloxacin-based sequential regimen and found no statistically significant advantage for either approach, with eradication rates of 84 percent and 81.3 percent respectively. The result carries practical weight for regions where antibiotic resistance is rising and susceptibility testing remains out of reach for most patients.

Helicobacter pylori infects an estimated half of the world’s population and remains highly prevalent across the Eastern Mediterranean region. The bacterium colonizes the gastric mucosa, where it drives chronic inflammation and, in a subset of those infected, progresses to peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, or adenocarcinoma of the stomach. Eradicating the organism is therefore not merely a matter of relieving dyspepsia; it is a recognized cancer-prevention strategy. Yet the standard triple therapy that dominated H. pylori treatment for decades, a proton pump inhibitor combined with clarithromycin and amoxicillin, has been losing ground worldwide as clarithromycin resistance has climbed, and in Syria the decline has been compounded by antibiotic misuse, disrupted healthcare infrastructure, and limited access to diagnostic resources.

When clarithromycin-based regimens fail or cannot be relied upon, clinicians frequently turn to levofloxacin, a fluoroquinolone antibiotic, as the backbone of alternative combinations. Two such combinations were tested in this trial. The concomitant regimen delivers a proton pump inhibitor, levofloxacin, amoxicillin, and a fourth agent simultaneously for the full 14 days, so the patient takes all drugs at once throughout the treatment period. The sequential regimen splits the therapy into phases: one antibiotic pairing is given first, followed by a second pairing, with the theoretical rationale that an initial phase of amoxicillin reduces bacterial load and damages cell walls in a way that may improve the effectiveness of the subsequent phase while limiting the window in which resistance can emerge.

Sequential therapy has been promoted in some settings as a way to sidestep clarithromycin resistance, and it has been studied extensively in Europe and Asia, but it had never been formally evaluated in Syrian patients. The researchers, led by Marouf Alhalabi of Damascus Hospital together with colleagues at Ibn Al-Nafees Hospital and the Syrian Board in Gastroenterology, designed a single-center, prospective, open-label, randomized superiority trial to answer the question directly under local conditions. The trial was prospectively registered on ClinicalTrials.gov as NCT06065267 on October 3, 2023, and received ethics approval from the Damascus Hospital and Ibn Al-Nafees Ethics Committee under approval number 41/23.

The study enrolled 150 adults with histologically confirmed H. pylori infection, all of whom had never previously received eradication therapy. Participants were assigned equally, 75 to each arm, to either the concomitant or the sequential levofloxacin-based regimen, each lasting 14 days. The primary outcome was eradication success, confirmed by a negative stool antigen test performed six weeks after the completion of therapy, a timing chosen to allow residual bacterial antigen to clear and to avoid false-positive results. The analysis followed the intention-to-treat principle, meaning every randomized patient was counted in the group to which they were assigned regardless of whether they completed the full course, an approach that preserves the real-world validity of the comparison by accounting for dropouts and imperfect adherence.

The numbers told a story of near-equal performance. Concomitant therapy eradicated the infection in 63 of 75 patients, an intention-to-treat rate of 84 percent, while sequential therapy succeeded in 61 of 75, or 81.3 percent. The absolute risk difference was 2.7 percentage points, with a 95 percent confidence interval spanning from minus 9.4 to 14.8, and the comparison yielded a p value of 0.83 with an odds ratio of 1.20, corresponding to a confidence interval of 0.516 to 2.81. In plain terms, the data provide no evidence that one regimen outperforms the other, and the confidence interval is wide enough that a modest advantage in either direction cannot be excluded. The authors were careful to state that the absence of a statistically significant difference does not establish equivalence or non-inferiority, a distinction that matters in clinical trial interpretation: proving two treatments equal requires a trial designed and powered for that purpose, which this superiority trial was not.

Both regimens were generally well tolerated, an important consideration given that eradication therapy requires patients to take multiple medications daily for two weeks. Nausea was the most frequently reported adverse event in both groups, followed by anorexia, headache, a persistent bitter taste, and skin rash. There was no significant difference in the frequency of adverse events between the two arms, suggesting that the added complexity of the sequential schedule does not buy any tolerability advantage. Baseline characteristics of the two groups were comparable, reducing the likelihood that imbalances in age, sex, or disease profile skewed the outcome.

The findings arrive against a backdrop of genuine clinical constraint. In settings where culture and susceptibility testing are unavailable, clinicians must prescribe empirically, choosing regimens based on regional resistance data and local experience rather than on the resistance profile of an individual patient’s infection. Syria’s healthcare system has been strained by years of conflict and economic crisis, and the authors note that susceptibility-guided therapy and many of the internationally recommended first-line regimens may simply be unavailable. In that context, levofloxacin-based empirical therapy remains in use, and the question of which levofloxacin-based strategy to choose is not academic. The trial suggests that when such therapy is required, the simpler concomitant regimen may offer practical advantages: a single, uniform dosing schedule for 14 days is easier to explain, easier to follow, and less prone to the confusion that phased regimens can introduce, with no measurable cost in effectiveness.

The moderate eradication rates observed in both arms, in the low-to-mid 80 percent range, also serve as a reminder that levofloxacin resistance itself is a growing problem in many regions, and that no empirical regimen can be assumed to work indefinitely. The authors emphasize that these findings should be interpreted in light of local resistance patterns and healthcare limitations, and they call for further multi-center studies that incorporate antimicrobial susceptibility testing. Such studies would allow clinicians to match therapy to the actual resistance profile of circulating H. pylori strains, an approach that international guidelines increasingly favor but that remains aspirational in much of the Eastern Mediterranean.

For the broader field, the trial adds a data point from a population that is rarely represented in H. pylori treatment literature. Most eradication trials are conducted in East Asia, Europe, or North America, where resistance patterns, drug availability, and patient populations differ substantially from those in conflict-affected or resource-limited settings. Demonstrating that a straightforward four-drug concomitant regimen achieves roughly 84 percent eradication in treatment-naïve Syrian patients, and that a more complex sequential schedule offers nothing extra, gives local clinicians an evidence-based reason to favor simplicity. As antibiotic resistance continues to erode the effectiveness of legacy regimens worldwide, trials like this one, grounded in the realities of a specific healthcare environment rather than in idealized conditions, are becoming an essential complement to guideline committees’ recommendations.

Subject of Research: A randomized trial comparing levofloxacin-based concomitant and sequential therapies for Helicobacter pylori eradication in treatment-naïve Syrian patients.

Article Title: Levofloxacin-based concomitant versus sequential therapy for Helicobacter pylori eradication in treatment-naïve Syrian patients: a randomized trial showing no superiority of sequential therapy

Article References: Alhalabi, M., Alshiekh, H. A., Sheikh Alhara, A. A., Ismail, A. A., Shehab, W., & Osamah, W. (2026). Levofloxacin-based concomitant versus sequential therapy for Helicobacter pylori eradication in treatment-naïve Syrian patients: a randomized trial showing no superiority of sequential therapy. Gut Pathogens. https://doi.org/10.1186/s13099-026-00881-x

Image Credits: AI Generated

DOI: 10.1186/s13099-026-00881-x

Keywords: Helicobacter pylori, levofloxacin, concomitant therapy, sequential therapy, eradication therapy, antibiotic resistance, randomized clinical trial, Syria, gastroenterology, stool antigen test, fluoroquinolone, clinical trial